Glioma-targeting Adenovirus Vector Construction Service
Malignant gliomas such as glioblastoma are the most common and lethal intracranial tumors. These cancers exhibit a relentless malignant progression characterized by widespread invasion throughout the brain, destruction of normal brain tissue, and certain death. In the past decade, gene therapy of tumors has gained credence, particularly in glioma management, as these tumors are not completely resectable and tend to micro-metastasize. Adenoviral vectors have advantages over other viral vectors in that they are relatively non-toxic and do not integrate in the genome. Creative Biolabs has been occupied in the research of gene therapy for years and focuses on the field of human diseases research with a professional adenovirus vector construction platform that can help you with gene therapy development.
Introduction of Glioma-targeting Adenovirus Vector
The gene therapy approach, using adenovirus-mediated Herpes simplex virus thymidine kinase (HSV-tk), entered into clinical trials of glioma treatment in the 1990s, and thus far it has become a popular application. HSV-tk is the prototypes of cytotoxic suicide gene-based therapies where a two-component system induces cytotoxicity. HSV-tk coupled with intravenously administered ganciclovir (GCV) have been the most effective approaches. The delivery of the HSV-tk gene has been performed by using either stereotactic intratumoral injections or intraoperative injections into the wound bed. The HSV-tk enzyme expressed by the HSV-tk is capable of converting GCV into a monophosphate. Once a monophosphate is converted into a GCV-triphosphate by cellular enzymes, it is then incorporated into replicating DNA by cellular DNA polymerases. However, GCV-triphosphates are not compatible substrates for chain elongation, and DNA replication is terminated resulting in cell death. In addition, on the basis of animal experiments, >10% transduction efficiency is required to achieve a therapeutic effect using HSV-tk gene therapy. It has been reported that high-titer adenovirus results in a sufficient transduction efficiency in clinical situation.
Figure 1. Mechanism of adenovirus vectors encoding HSV-tk. (Castro, 2014)
Service
In recent years, adenoviruses have become the most popular gene transfer vector, and some studies using adenovirus-mediated HSV-tk gene therapy have shown significant efficiency in clinical use. Optimization and modification of adenovirus vectors may improve the clinical effectiveness of gene therapy for gliomas. Therefore, we offer a large collection of adenovirus vector construction services covering the restoration of the function of mutated tumor suppressor genes, such as HSV-tk, p53, retinoblastoma gene (RB), p16, cytocine deaminase (CD), and phosphatase tensin gene (PTEN).
Figure 2. Adenovirus vector: potential therapeutic for glioma. (Manikandan, 2019)
Creative Biolabs has long-term devoted to the development of gene therapies for years. With extensive experience, our scientists have developed several adenovirus vector construction platforms to promote customers' project goals. We are pleased to use our advanced platforms to offer the best service and the most qualified products to satisfy diverse needs from our customers. If you are interested in our services, please contact us for more details.
References
- Castro, M.G.; et al. (2014). Adenoviral vector-mediated gene therapy for gliomas: coming of age. Expert Opinion on Biological Therapy. 14(9):1241-1257.
- Manikandan, C.; et al. (2018). Viral vector: potential therapeutic for glioblastoma multiforme. Cancer Gene Therapy.
